Menopause Without Pills: Rethinking Hot Flashes

By GINA KOLATA

his article was reported by Gina Kolata, Milt Freudenheim and Robin Marantz Henig and was written by Ms. Kolata.

In the few months since a study of a widely used hormone regimen found that its risks outweighed its benefits, the prevailing view of menopause has undergone a momentous shift.

For decades, women have been told that the symptoms of menopause — hot flashes and night sweats as well as vaginal dryness that could make sex a painful ordeal and libido a distant memory — were burdens they should not have to bear. With hormone therapy, they would feel like the clock was turned back. At the same time, they could protect themselves against osteoporosis, and probably even reduce their risk of heart attacks and strokes.

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When the study, known as the Women's Health Initiative, was halted in July, many doctors changed their message. Try to live with your symptoms, these doctors now say. Or find other ways to deal with them. And forget about using hormones solely to protect yourself from diseases; there are other, better ways.

It is an almost unheard of transformation of the medical landscape, said Dr. Barbara J. Turner of the University of Pennsylvania, who studies the pace of innovation. Doctors "turned on a dime," she said.

But it is impossible to tell how many patients turned with them, and what happened when they did.

There is no obvious pattern of responses to the new reality. In interviews, gynecologists and internists say some patients have stopped taking hormones, only to resume their use when they find symptoms intolerable. Others say most women who stop taking the pills have little or no trouble. They note that even before the study was halted last summer, more than half of the women who started hormone therapy stopped it on their own within a few years.

Still other doctors are devising their own methods of weaning women from the drugs — suggesting they wear estrogen patches and gradually trim them down to nothing, or increase the interval between pills. In this, however, they are acting on their own. There are no practice guidelines, no rigorous studies on what works best.

Eventually, the Women's Health Initiative will have data on how its participants fared when they were advised to stop taking their hormone pills. For now, the only data come from drug company sales figures, which show that many women taking Prempro, the hormone combination made by Wyeth that was tested in the study, have stopped, their number falling to 1.5 million from 2.7 million.

But in Wyeth's loss, other companies see an opportunity. For example, sales of Evista, made by Eli Lilly & Company, rose by 24 percent in September. Evista, which can actually elicit hot flashes but protects bone, has some estrogenlike properties, but the company emphasizes that it is not a hormone.

"There's this whole open market," said Valerie Layne, a nurse practitioner at Hightstown Medical Associates, a private practice in New Jersey where she says the Eli Lilly sales representative is now a frequent visitor. "They know our alternative now is their drug," Ms. Layne said. "Even though hormone therapy may be O.K., everyone is too afraid to continue."

The Burst Bubble

The study that caused this uproar, the Women's Health Initiative, involved 16,000 women who were randomly assigned to take either Prempro, a popular combination of estrogens and progestin, or a placebo. The researchers halted the study prematurely when the accumulating data indicated that even though hormone therapy can reduce cholesterol levels, women who took Prempro had slightly more heart attacks, strokes and blood clots. They also had slightly more breast cancer. These risks exceeded the regimen's benefits, of slightly less colon cancer and slightly fewer fractures.

Women who were taking Prempro were advised to stop taking the pills immediately, and the scientists said there was no reason to believe that the findings applied only to Prempro. Until proven otherwise, they said, women and their doctors should assume that all hormone therapy that involved estrogen and progestin bears the same risks.

The study did not test other hormone regimens, but many researchers say it cannot be assumed that they are any safer.

At first, many doctors, gynecologists in particular, reacted with anger and denial.

"We have had a real love affair with hormone therapy," said Dr. Susan L. Hendrix, a study investigator and gynecologist at Wayne State University in Detroit. When the study said it might not be a panacea, "it was like telling someone they have an ugly baby."

Dr. Isaac Schiff, who is the chairman of obstetrics and gynecology at Massachusetts General Hospital in Boston, said it was his impression that many gynecologists were upset because their own clinical experience had told them that the drugs were a boon to women. Internists, he added, who had been prescribing hormone therapy to prevent conditions like heart disease and osteoporosis, tended to be more accepting of the study's findings.

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Dr. Schiff explained: "As a gynecologist, you have a patient who comes into your office who is troubled with hot flashes or she has severe vaginal atrophy and she says sex is not pleasurable. You prescribe hormone therapy and she comes back four months later and says, `Oh, doctor, I feel so much better.' An internist does not have someone come back and say, `Thank you, doctor, my heart feels better.' "

Yet many gynecologists, even those who say they think hormone therapy has been demonized, say they have changed their message.

"In the old days, I used to say, `Look, there's no evidence that this is going to hurt you,' " said Dr. Andrew Good, a gynecologist at the Cleveland Clinic. "Now I can't say that with the same enthusiasm."

Dr. Jan L. Herr, a gynecologist at Kaiser Permanente Medical Group in San Rafael, Calif., said the new message has meant that women have had to change their expectations of life in their middle years. She asks women who find their symptoms of menopause unbearable to try the lowest possible dose of hormone therapy, which may not rid them of their symptoms.

"They have to be satisfied with feeling better, but not perfect," Dr. Herr said. "They had always wanted to feel perfect," with no hot flashes, no night sweats, no vaginal dryness. "They had always said, `Why should I feel like I'm 55? I want to feel like I'm 30.' " Now, she said, women have to get used to feeling as if they are 55.

'Honey, It's the Hormones'

Iretta Taylor, a customer service adviser in Houston, said she tried to live without hormone therapy but decided she would rather not.

Ms. Taylor, 49, explained: "I went into menopause at a very early age, at about 40, and it was a very bad, very emotional time. I was edgy, depressed, I thought I was having a nervous breakdown. I had hot flashes, too, and a hollow, dry look, and dryness in the vaginal area, which was no fun.

"As soon as I started taking H.R.T., it all went away," she said, referring to hormone therapy by its old name, H.R.T., for hormone replacement therapy. "A co-worker told me, `Your skin looks so fine.' It did; I had a real glow.

"When I heard all the horror stories last summer I stopped," she said. "I didn't even call my doctor; I just stopped. Right away I started to feel bad again. I thought at first that it was psychosomatic, but then I realized, `Honey, it's the hormones.'

"I asked my doctor, `Please put me back on H.R.T.,' and he did." Now, she said: "I feel like a woman is supposed to feel. If they ban this in the United States, I'll drive down to Mexico to get it. That's how much I need my H.R.T."

The question is, Are women like Ms. Taylor the exception or the rule?

"It's very clear that there is some proportion of women who did not react well to cold turkey," said Dr. Marcia L. Stefanick of Stanford University, who as principal investigator for the Women's Health Initiative lectures about the study and its results. "They are very vocal. But then I ask the audience, How many of you went cold turkey and had no problem whatsoever?" She is finding that "the vast majority of women are doing fine."

Dr. Herr turns to data from the days when she and others urged all women to take hormones. After two years, she said, 80 percent were not taking the drugs — they simply stopped filling their prescriptions. That tells her, she said, that many women are not bothered by severe symptoms, or choose to live with them. Doctors, she added, are more likely to hear from the women about their difficulties, which can skew their perspective.

They may not see women like Elizabeth Benney, who is 69 and runs a horse farm in Upton, Mass. She never had a hot flash, never had a night sweat, but started taking hormones about 15 years ago to alleviate vaginal dryness and avert osteoporosis, worried because her mother had had the disease. She feared that if her bones thinned and she was thrown from a horse, they might fracture.

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Last July, "when the news came out," she said, "I decided to stop." She did so with some reluctance, worried that the vaginal dryness would return and that her skin might age without the hormones. To her surprise, nothing happened. She feels and looks fine — no different, she says, from when she was taking the pills. Her bone density is fine, she added, so she does not appear to be at risk for fractures.

Doctors say some women are remaining on estrogen because they believe it keeps their skin looking young. The studies, so far, "are not nearly as well done as one would like," said Dr. Barbara A. Gilchrest, chairman of the dermatology department at the Boston University School of Medicine. But, Dr. Gilchrest said, there is credible evidence that hormone therapy can thicken skin by increasing the amount of collagen, or prevent its loss. It is not clear when questions about these or other possible uses of hormone therapy will be answered. Some studies, like ones asking if the therapy protects against Alzheimer's disease, are continuing. But given the findings so far, there is some question of whether it would be ethical to conduct studies of cosmetic uses. Many women, however, are already convinced.

"You wouldn't believe how many women want to stay on estrogen for their skin," said Dr. Margaret M. Polaneczky, a gynecologist at the Iris Cantor Women's Health Center in New York. "You could have an hourlong intellectual discussion about all the risks and benefits of hormone replacement therapy, about how it might be better to consider some other drugs for, say, osteoporosis prevention, and you think you've both agreed. But just as you're getting ready to write a prescription for Fosomax, she'll say, `Wait a minute — I've changed my mind. I think the estrogen is making my skin look younger. I'm going to stay on it.' "

Some can wean themselves from hormones only gradually, using schemes their doctors invented. Some doctors ask women to try doing without hormones on weekends, gradually extending the hormone-free days into the week. Others advise taking a pill every other day for a few weeks, then every third day, gradually going down to no pills at all. Dr. Hendrix prescribes hormone patches and tells women to cut them each week, snipping them down until there is nothing left.

"Is there any science to this?" Dr. Hendrix asked. "Absolutely not. We're on a rapid learning curve."

The Alzheimer's Hypothesis

Dr. Rowan T. Chlebowski of the Harbor-U.C.L.A. Research and Education Institute, an investigator with the Women's Health Initiative, has been spending time talking to doctors about what the study's data mean, and how to go on from here. His experience, he says, is a window on the lingering confusion. While the initial message is clear — that women should be asking themselves why they are taking hormones rather than why they are not taking them — it is overlaid with all sorts of what if's.

What if a woman takes hormones for only a year or so and then stops? The answer is, no one knows, Dr. Chlebowski said. "It is almost certain your risk will be reduced, but then it's a question of, well, what is the risk compared to the benefits?"

What if, doctors ask, they sit down with a woman and figure out what her risks are? They could suggest to women at risk of breast cancer or heart disease that they try to do without hormone therapy and advise that women at risk for colon cancer or osteoporosis take it.

If only it were so simple, Dr. Chlebowski said. One problem, he said, is that there is no reliable way to determine which women are at particular risk for specific diseases, whether it is breast cancer, heart disease, osteoporosis or colon cancer.

"There's a kind of assumption that a doctor can chat with you about your risk — Did your mother have a heart attack? — and that that would have an influence on what you're doing." The problem, he said, is that "our current methods don't do very well" in predicting risk.

Some doctors also wonder if there might be critical periods when estrogen might protect against heart disease, osteoporosis or Alzheimer's.

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While there are drugs to protect against heart disease and osteoporosis, there is nothing yet to prevent Alzheimer's. So if the window-of-opportunity hypothesis has any urgency, it might be with that disease.

"I think it is the most compelling reason to take estrogen," said Dr. Stanley Birge, a gerontologist at Washington University in St. Louis.

But other experts say that at this point it is simply wishful thinking to say that estrogen therapy is protective, but only if it is started early. Nevertheless, some women say that for now they will accept hormone therapy's small excess risk in hopes that by starting therapy early they will gain a potentially large benefit.

The Alzheimer's hypothesis "is a supposition," said Dr. Deborah Grady, who directs the University of California San Francisco/Mount Zion Women's Health Clinical Research Center.

While some laboratory and animal studies have indicated that hormone therapy might protect brain cells, it is not clear what would be required to prevent Alzheimer's. In some studies, like one published last week, women who were taking hormones had less Alzheimer's disease, but in others they did not. Dr. Grady said that in several studies, women who took estrogen actually performed worse on cognitive tests.

But Dr. Stefanick said that until researchers completed rigorous studies asking if estrogen can protect against Alzheimer's disease, the question will linger.

"Alzheimer's disease is what people are going to hold onto," she said. "Everyone is afraid of losing their memory. Until we get the answer to that one, there will always be that last little piece."